The myelin-associated glycoprotein (MAG) is localized in the periaxonal membranes of PNS and CNS myelin sheaths where it appears to be involved in glia-axon interactions. Structural information about MAG obtained from sequencing of cDNA clones from rat brain indicates that is has a single transmembrane domain separating two different developmentally regulated C-terminal tails generated by alternative splicing of the primary mRNA transcripts from a heavily glycosylated N-terminus containing five domains that are related in sequence to each other and to molecules in the immunoglobulin superfamily such as neural cell adhesion molecule. The C-terminal domains have several potential phosphorylations sites, and it was demonstrated that both CNS and PNS MAG are phosphorylated from inorganic phosphate in tissue slices and from ATP by kinases in purified myelin. The expression of MAG in cultured oligodendrocytes, C6 glioma cells, and Schwann cells, is being investigated with the ultimate objectives of identifying factors that control its synthesis and probing its function in cell-cell interactions. In multiple sclerosis, MAG is reduced more than proteolipid protein (PLP) or myelin basic protein in periplaque areas, and in many lesions much as of the MAG is in the form of its proteolytic derivative, dMAG. A carbohydrate epitopes(s) in human MAG and other glycoconjugates is the target for monoclonal IgM in neuropathy associated with gammopathy. Sequencing of cDNAs for human MAG is in progress and shows more than 95% homology with rat MAG and the existence of an additional, potential glycosylation site. Further, characterization of the human cDNA may reveal properties that re relevant to human demyelinating diseases. A correlation between serum antibodies to GM1 ganglioside and motor symptoms in both the paraproteinemia and chronic inflammatory polyneuropathies suggests that antibodies to GM1 could have pathogenic effects on motor nerves. Jimpy mutant mice can form compacted myelin sheaths in the absence of PLP, but the structure of the intraperiod line is abnormal.